PMID: 9523565Apr 2, 1998Paper

Suppression of astroglial nitric oxide synthase expression by norepinephrine results from decreased NOS-2 promoter activity

Journal of Neurochemistry
D L Feinstein

Abstract

We previously demonstrated that norepinephrine (NE) inhibits induction of the calcium-independent isoform of nitric oxide synthase (NOS-2) in primary rat astrocyte cultures. However, the molecular mechanisms underlying this effect are unknown. In C6 cells and astrocytes, NE suppressed both cytokine- and lipopolysaccharide (LPS)-dependent nitrite accumulation, an index of NOS-2 activity. NE reduced the steady-state levels of NOS-2 mRNA induced by LPS plus cytokines but did not decrease NOS-2 mRNA stability or inhibit activation or subunit composition of transcription factor nuclear factor kappaB, which is necessary for NOS-2 induction. In C6 cells stably transfected with a 1,588-bp mouse NOS-2 promoter, NE reduced LPS plus cytokine-induced reporter gene expression, suggesting inhibition of NOS-2 promoter activity. In contrast, suppression was lost when a truncated 85-bp NOS-2 promoter was used, and in these cells NE potentiated reporter gene expression, alone or in the presence of LPS and cytokines. These results suggest that the suppressive effects of NE are due to modification of transcription factor activity in a region located between -1,588 and -85 of the NOS-2 promoter and may help explain observations that in some cells c...Continue Reading

Citations

Jun 7, 2002·The Journal of Biological Chemistry·Vitaliy GavrilyukDouglas L Feinstein
Feb 6, 2010·Journal of Neurochemistry·Scott E Counts, Elliott J Mufson
Dec 14, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E Galea, D L Feinstein
Jun 15, 2006·Antioxidants & Redox Signaling·Sergey KalininDouglas L Feinstein
Jan 5, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Melissa CambronJacques De Keyser
Mar 25, 2018·Neurotoxicity Research·Meng-Yang Zhu
Feb 3, 1999·Molecular Pharmacology·D L FeinsteinS Regunathan
Aug 15, 2002·Neurochemistry International·Douglas L FeinsteinElena Galea
May 20, 2003·Biochemical Pharmacology·Elizabeth MazzioKaram F A Soliman
Feb 16, 2005·Biochemical Pharmacology·Dalya Abdulla, Kenneth W Renton
Feb 9, 2010·Progress in Neurobiology·Guy LaureysJacques De Keyser

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